In the present study, we focused on the circular form of the TP53 gene, and discovered that its coding product, circp53–209aa, can competitively interact with CypD from the CypD/TRAP1/HSP90 complex, leading to the activation of its isomerase activity and the induction of mPTP opening in both TP53 mutant and nonmutated tumor cells. Here, TP53 is linked to neoplasm.